Contribution of the cadaveric recirculation system in the anatomical study of lymphatic drainage of the ovary: applications in the management of ovarian cancer.

PURPOSE: The present knowledge about lymphatic drainage of the ovary is based on carcinological studies, but it has only rarely been studied under physiological conditions. However, it is one of the preferential routes of dissemination in ovarian cancer, and understanding it is therefore vital for optimal carcinological management.Our purpose was to evaluate the feasibility of an innovative technique to study the lymphatic drainage territories of the ovary using a recirculation module on the cadaveric model. METHODS: We injected patent blue into the cortex of twenty "revascularised" cadaver ovaries with the Simlife recirculation model. We observed the migration of the dye live and described the drainage territories of each ovary. RESULTS: We observed a staining of the lymphatic vessels and migration of the dye in all the subjects, systematically ipsilateral to the injected ovary. We identified a staining of the lumbo-aortic territory in 65% of cases, with a preferential lateral-caval involvement (60%) for the right ovary and lateral-aortic territory (40%) for the left ovary. A common iliac involvement was observed in only 10% of cases. In 57% of cases, the staining of the lumbo-aortic territory was associated with a staining of the suspensory ligament. The pelvic territory was involved in 50% of cases, with an external iliac staining in 25% of cases and internal in 20%. CONCLUSION: Our study provides for a better understanding of lymphatic drainage of the ovary using a new detection method, and allows the possibility of improving the teaching for operators with a realistic model. Continuation of this work could lead to considering more targeted and thus less morbid lymph node sampling for lymph node staging in early-stage ovarian cancer.

New Strategy for Breast Cancer Related Lymphedema Treatment by Endermology: ELOCS Phase II Randomized Controlled Trial.

BACKGROUND: This phase II trial sought to be the first of its kind to estimate the success rate of endermology in reducing breast cancer-related lymphedema. PATIENTS AND METHODS: ELOCS is a French, monocentric, randomized, open-label phase II trial. Patients were randomized to receive the following over a 5-day treatment period: standard intensive decongestant treatment (IDT) (bandages and manual lymphatic drainage MLD) (group 1); IDT including bandages, MLD, and Cellu M6 (group 2); and IDT including bandages and Cellu M6 (Group 3). The main endpoint was the success rate in each group, (reduction of at least 30% in the excess volume). We estimated that endermology treatment (groups 2 and 3) would be of interest successes occurred in at least 21 out of 31 patients. RESULTS: A total of 93 patients were included (31 patients in each of the 3 groups). The median age was 64.5 years (IQR: [56.4-71.3]). Patients were treated with mastectomy (n = 35), axillary lymphadenectomy (n = 80), radiotherapy (n = 91), and chemotherapy (n = 68). The mean relative reduction in excess volume was 38% in group 1, 33% in group 2, and 34% in group 3. Success rate was 58.1% in group 1 (18/31, P = ,0237), 51.6% (16/31, P = ,5) in group 2, and 64.5% (20/31, P = ,075) in group 3. In the LPG groups (2 and 3), 10/62 (16%) patients found LPG painful and 9/62 (15%) patients considered it to be unpleasant. CONCLUSION: Even though the critical threshold of 21 successes was not met, this study was the first to validate a standardized and reproducible endermology protocol.

Postoperative ileus after digestive surgery: Network meta-analysis of pharmacological intervention.

AIMS: Several medicinal treatments for avoiding postoperative ileus (POI) after abdominal surgery have been evaluated in randomized controlled trials (RCTs). This network meta-analysis aimed to explore the relative effectiveness of these different treatments on ileus outcome measures. METHODS: A systematic literature review was performed to identify RCTs comparing treatments for POI following abdominal surgery. A Bayesian network meta-analysis was performed. Direct and indirect comparisons of all regimens were simultaneously compared using random-effects network meta-analysis. RESULTS: A total of 38 RCTs were included in this network meta-analysis reporting on 6371 patients. Our network meta-analysis shows that prokinetics significantly reduce the duration of first gas (mean difference [MD] = 16 h; credible interval -30, -3.1; surface under the cumulative ranking curve [SUCRA] 0.418), duration of first bowel movements (MD = 25 h; credible interval -39, -11; SUCRA 0.25) and duration of postoperative hospitalization (MD -1.9 h; credible interval -3.8, -0.040; SUCRA 0.34). Opioid antagonists are the only treatment that significantly improve the duration of food recovery (MD -19 h; credible interval -26, -14; SUCRA 0.163). CONCLUSION: Based on our meta-analysis, the 2 most consistent pharmacological treatments able to effectively reduce POI after abdominal surgery are prokinetics and opioid antagonists. The absence of clear superiority of 1 treatment over another highlights the limits of the pharmacological principles available.

The lymphatic system of the uterine cervix: towards a more precise definition of the drainage routes.

PURPOSE: Lymph node involvement in cancer of the uterine cervix is a major independent prognostic factor for overall survival. The aim of our study was to examine the lymphatic drainage regions of the different parts of the uterine cervix. METHODS: An anatomical study of fresh cadavers was conducted by injecting patent blue in the anterior or posterior lip of the uterine cervix and dissecting drainage regions. Furthermore, a retrospective radiological and pathological studies were conducted on patients who were treated for early-stage cancer of the uterine cervix with lymph node involvement. Radiological analysis of pre-therapeutic MRIs and/or pathological analysis of surgical specimens showed the precise location of the tumour. A correlation between the anatomy of the primary lesion site and the lymphatic area involved was established. RESULTS: We administered 15 cadaveric injections: 8 in the anterior lip of the uterine cervix and 7 in the posterior one. For 100% of the anterior lip injections, lymphatic drainage was bilateral ileo-obturator (n = 8/8) combined with bilateral parametrial drainage. For the posterior injections, there was never any ileo-obturator drainage, and 6 of the 7 (75%) posterior injections drained in the posterior uterine serosa. Concerning the clinical study, we included 21 patients. We observed a non-significant tendency towards bilateral lymph node involvement when the tumour of the anterior lip. CONCLUSION: Physiological lymphatic drainage of the uterine cervix presents anatomical specificities, depending on the structure studied, anterior or posterior lip of the cervix. Better knowledge of these specificities should allow personalized surgery for each patient.

Estrogen Actions in Placental Vascular Morphogenesis and Spiral Artery Remodeling: A Comparative View between Humans and Mice.

Estrogens, mainly 17ß-estradiol (E2), play a critical role in reproductive organogenesis, ovulation, and fertility via estrogen receptors. E2 is also a well-known regulator of utero-placental vascular development and blood-flow dynamics throughout gestation. Mouse and human placentas possess strikingly different morphological configurations that confer important reproductive advantages. However, the functional interplay between fetal and maternal vasculature remains similar in both species. In this review, we briefly describe the structural and functional characteristics, as well as the development, of mouse and human placentas. In addition, we summarize the current knowledge regarding estrogen actions during utero-placental vascular morphogenesis, which includes uterine angiogenesis, the control of trophoblast behavior, spiral artery remodeling, and hemodynamic adaptation throughout pregnancy, in both mice and humans. Finally, the estrogens that are present in abnormal placentation are also mentioned. Overall, this review highlights the importance of the actions of estrogens in the physiology and pathophysiology of placental vascular development.

PET-MRI for evaluation of response to radiochemotherapy in patients with locally advanced cervical cancer.

OBJECTIVE: We aimed to analyze the diagnostic test accuracy of positron emission tomography and a magnetic resonance imaging scan (PET-MRI) fusion in evaluating tumor response after radiochemotherapy in patients with locally advanced cervical cancer. METHODS: Patients treated at two institutes between January 2008 and December 2016 were studied retrospectively. Re-evaluation by positron emission tomography (PET) and magnetic resonance imaging (MRI) was performed in a non-concurrent way 4-8 weeks after treatment. A nuclear medicine doctor and a radiologist (subsequently referred as "radiologists"), both experts in gynecological oncology, re-examined the post-treatment MRI and positron emission tomography-computed tomography (PET-CT) separately, and then performed a fusion of these examinations. In this study we describe this "a posteriori fusion methodology", with two levels, enabling limitation of anatomical shifts. The gold standard was anatomical pathology analysis of the surgical specimen, since all patients underwent surgery following this radiological re-evaluation. The radiologists' degree of certainty in their diagnoses, and the impact of fusion on their diagnostic confidence were assessed by the radiologists, using two Likert judgment scales. They also adjudicated on possible changes of interpretation after the fusion. RESULTS: Thirty-one patients were included. The PET-MRI fusion has a sensitivity of 79% and a specificity of 90%. The positive predictive value (PPV) was 94%, and the negative predictive value (NPV) was 69%. In 45% of cases (n=13), radiologists reported an improvement in their degree of certainty in their diagnosis using a Likert judgment scale, due to inspecting the PET and MRI fused. A change in interpretation of tumor response was observed using a Likert judgment scale in 31% of cases. CONCLUSION: PET-MRI fusion improves the radiologist's own diagnostic confidence in assessing response to concurrent radiochemotherapy in locally advanced cervical cancer. More studies using a latest generation hybrid system will be necessary to further compare to MRI and PET-CT.

MRI and rectal endoscopy sonography performance to diagnose the digestive depth infiltration of pelvic endometriosis.

INTRODUCTION: The main objective of this study was to evaluate the performances of MRI and rectal endoscopy sonography (RES) in predicting the depth of bowel wall infiltration by deep infiltrating endometriosis (DIE). MATERIAL AND METHOD: We conducted a single center retrospective study from April 2014 to March 2020 including all patients who had undergone digestive tract resection (discoid or segmental) for DIE removal and who had benefited from full preoperative imaging workup based on both pelvic MRI and RES. RESULTS: Fifty two patients were enrolled in the study. Median age was 35.8 years (26.1-44.5 years). Indications for surgery mainly comprised chronic pelvic pain (94.2%) and infertility (36.5%). Overall, pathological examination showed digestive involvement in 92.3% of patients, while transmural infiltration was found in 38.4% of cases. In contrast, both MRI and RES suspected transmural involvement in 42 patients (80.8%). Corresponding sensitivity and specificity were 0.95 [95% CI (0.751-0.999)] and 0.28 [95% CI (0.137-0.467)], respectively. Our results revealed agreement between MRI and RES in 85% of cases with a kappa at 0.5 [95% CI (0.207-0.803), moderate agreement]. Subgroup analysis in patients with transmural MRI lesions showed a sensitivity of 0.95 [95% CI (0.740-0.999)] and a specificity of 0.13 [95% CI (0.028-0.336)]. CONCLUSION: Our study suggests that performing a second-line examination is not useful if there is no transmural impairment in MRI or RES. Nevertheless, the combination of these two preoperative examinations seems to be essential for the evaluation of the depth of digestive involvement of endometriosis to guide surgical management as effectively as possible. The constitution and training of multidisciplinary expert groups must be developed to be able to offer optimal patient management.

Study of postoperative complications after the implementation of a multidisciplinary care pathway for patients with digestive endometriosis.

PURPOSE: To assess the quality of care following the establishment of a multidisciplinary care pathway for patient operated on for deep pelvic endometriosis with digestive impairment. METHODS: We conducted a retrospective monocentric study of patients suffering from deep infiltrating endometriosis, treated in Gynaecological Department at Toulouse University Hospital from January 2018 to December 2020. We compared our results to those of our previous study, Gornes et al. which showed a postoperative complication occurred in 37.8% of the cases and a postoperative severe complication according to the Clavien-Dindo classification (grades 3b) rate of 18.3%. RESULTS: 98 patients were included. Our study shows a clear decrease in postoperative complications with an overall complication rate of 19.4% and severe complications (grades 3b) of 4.1%. The rate of complication appeared to be significantly less frequent in the case of shaving in relation to other digestive procedures (p = 0.008) and in the case of a lesion of < 20 mm by MRI (p = 0.01). The use of multidisciplinary surgical care was more frequent in the case of multiple locations (66.7% vs. 41.8%, p = 0.07) and was more frequent in the case of transmural damage with echo endoscopy (and to a lesser degree in the case of damage of the muscularis or mucous membrane) (p = 0.05). CONCLUSIONS: Multidisciplinary care of endometriosis with digestive damage appears to be indispensable. The intraoperative intervention of a skilled digestive surgeon of bowel endometriosis helps create the best balance between effectiveness-complications-functional prognosis, with a reduction of severe postoperative complications.

Boot camp approach to surgical residency preparation: feedback from a French university hospital.

INTRODUCTION: The transition from medical student to surgical resident is not a simple one. The aim of this study was to report the experience of a university hospital in the organization of the induction course for future surgical residents and the contribution of a video support in the learning of the suture. MATERIAL AND METHOD: We were able to study two consecutive years of students (October 2020 and 2021). Concerning the practical and technical workshops (learning suture) we carried out a comparative study between two groups of students. A group that had video support for learning suture (video group) and a group without video (control group). The evaluation of the suture was performed in a blinded manner by two supervising surgeons. The other practical workshop was drain fixation; the students did not have a video for this workshop. A comparative study was also performed for the drain fixation workshop between the two groups (video group and control group). A program of theoretical courses was also set up. This program is established according to the different future functions of the residents by integrating medico-legal notions and teamwork. Satisfaction questionnaires were given to the students and the answers were given two months after taking up their duties in the hospital (6 questions with Likert scale and 4 free questions). RESULTS: The cohort consisted of 58 students (29 each in 2020 and 29 in 2021). Comparative analyses of the evaluation of the suture workshops showed better performance in the video group compared with the group without video. The comparison of these two groups did not show significant differences in the drain fixation workshop. The theoretical teaching was broken down according to the students' future tasks and each speaker was a specialist in his or her field of expertise. The results of the questionnaires showed a desire on the part of the students to increase the time spent on practical workshops and theoretical forensic teaching. CONCLUSION: We were able to show through these two years of a program that we were able to offer a surgical resident preparation course. In addition, we have highlighted the contribution of a video support in the learning curve of the suture.

Transvaginal minimally invasive approach: An update on safety from an anatomical, anatomopathological and clinical point of view.

INTRODUCTION: The aim of this work was to analyze the transvaginal approach in minimally invasive surgery in terms of anatomical, histopathological and functional characteristics, to show the safety of this surgical approach. METHODS: Anatomical study was first conducted by dissection on fresh cadavers of adult women in order to measure the distance between the vaginal incision and the ureters, rectum and hypogastric nerves. In parallel, an anatomopathological study detailed and compared the macroscopic and histological characteristics of the anterior and posterior surfaces of vaginal samples obtained from cadavers and patients in the context of a hysterectomy for benign pathology. Finally, patients who underwent a transvaginal approach nephrectomy or transplantation were retrospectively enrolled for a clinical examination and an evaluation of their sexuality. RESULTS: The anatomical study conducted on seventeen cadavers showed that the posterior vaginal fornix was remote from the major structures of the pelvis such as rectum, ureters, hypogastric plexus, which allowed a safe incision. Mechanical tests further demonstrated that the posterior vaginal fornix was more extensible than the anterior and histological features showed no major vascular or nervous structures. Ten patients were included in the retrospective clinical study. Long-term follow up showed no negative impact on the texture of the vagina or satisfaction from sexual intercourse. CONCLUSIONS: Anatomical, histological and functional data supported that transvaginal approach by posterior vagina fornix incision is a minimally invasive surgery that can be performed safely and effectively by a skilled surgeon in cases with a specific surgical indication for this approach.

Prognostic value of lymphovascular space invasion in early-stage cervical cancer.

OBJECTIVE: Few prognostic factors likely to influence therapeutic management of early-stage cervical cancer are currently recognized. The objective of this study was to determine the prognostic value of lymphovascular space invasion (LVSI) in overall survival of patients with early-stage cervical cancer. METHODS: This is a retrospective study of patients treated for early-stage cervical cancer between January 1996 and December 2013 at Toulouse University Hospital and the Cancer Center Claudius Regaud Institute. Patients were included if they had FIGO 2018 stage IA1, IA2, IB1/2, or IIA1 cervical cancer. All patients had to have had surgery (conization, radical hysterectomy, or radical trachelectomy). The presence of LVSI was evaluated in the initial anatomic pathology reports of the excised tissue. The presence of LVSI was defined by the presence of epithelial tumor cells in the lumen of vessels, lined by endothelial cells. If the data were missing, the slides were reviewed by an expert pathologist. Comparative analyses of patient populations with and without LVSI invasion were performed, as well as analyses of overall and disease-free survival. RESULTS: A total of 158 patients were included in the analysis. Seventy-two (45.6%) patients had LVSI. More patients with LVSI received external radiotherapy in addition to standard treatment than patients without LVSI (53% vs 14%, p<0.0001). The overall survival of patients with LVSI (89.8%) was similar to that of patients without LVSI (91.5%) (p=0.39). For patients without lymph node involvement but with LVSI, disease-free survival at 5 years tended to be higher among those treated with external radiotherapy in addition to standard treatments (92.6% vs 79.8%, difference not tested due to the small number of events). CONCLUSION: Patients with early-stage cervical cancer with LVSI received external radiotherapy more often, and therefore had an overall survival at 5 years identical to patients without LVSI.

Rationale for opportunistic salpingectomy during gynecological surgery for a benign condition: A review of the available literature.

INTRODUCTION: Recent discoveries have shed light on the benefits of opportunistic salpingectomy in the prevention of ovarian cancer. However, in this time of increasing interest in the parameters of ovarian reserve, there are no national recommendations on the subject. This literature review provides an enlightened look at the rationale for performing an opportunistic salpingectomy. OBJECTIVES: To evaluate the benefits and risks associated with opportunistic salpingectomy during surgery for a benign gynecological condition. MATERIAL AND METHODS: We carried out a systematic review of the literature using the Pubmed/Medline search engine and the Cochrane database. RESULTS: A total of 61 articles were selected from over 300 references. The protective impact against cancer, which is widely demonstrated in the literature, is proof of the benefit of this procedure. Furthermore, no increase in intraoperative morbidity has been noted. However, the clinical impact on the ovarian reserve remains uncertain (in particular the occurrence of early pre-menopausal symptoms during the perimenopausal period). Nonetheless, the socioeconomic analysis supports performing opportunistic salpingectomy. CONCLUSION: Performing opportunistic salpingectomy does not appear to cause an increase in morbidity but the impact on ovarian function is uncertain. The fact that there is a proven benefit of such a procedure against cancer indicates that prior to any surgery a clear discussion should be held with the patient in which they should be fully informed.

Estrogen Receptors and Endometriosis.

Endometriosis is a frequent and chronic inflammatory disease with impacts on reproduction, health and quality of life. This disorder is highly estrogen-dependent and the purpose of hormonal treatments is to decrease the endogenous ovarian production of estrogens. High estrogen production is a consistently observed endocrine feature of endometriosis. mRNA and protein levels of estrogen receptors (ER) are different between a normal healthy endometrium and ectopic/eutopic endometrial lesions: endometriotic stromal cells express extraordinarily higher ERß and significantly lower ERα levels compared with endometrial stromal cells. Aberrant epigenetic regulation such as DNA methylation in endometriotic cells is associated with the pathogenesis and development of endometriosis. Although there is a large body of data regarding ERs in endometriosis, our understanding of the roles of ERα and ERß in the pathogenesis of endometriosis remains incomplete. The goal of this review is to provide an overview of the links between endometriosis, ERs and the recent advances of treatment strategies based on ERs modulation. We will also attempt to summarize the current understanding of the molecular and cellular mechanisms of action of ERs and how this could pave the way to new therapeutic strategies.

Membrane expression of the estrogen receptor ERα is required for intercellular communications in the mammary epithelium.

17ß-Estradiol induces the postnatal development of mammary gland and influences breast carcinogenesis by binding to the estrogen receptor ERα. ERα acts as a transcription factor but also elicits rapid signaling through a fraction of ERα expressed at the membrane. Here, we have used the C451A-ERα mouse model mutated for the palmitoylation site to understand how ERα membrane signaling affects mammary gland development. Although the overall structure of physiological mammary gland development is slightly affected, both epithelial fragments and basal cells isolated from C451A-ERα mammary glands failed to grow when engrafted into cleared wild-type fat pads, even in pregnant hosts. Similarly, basal cells purified from hormone-stimulated ovariectomized C451A-ERα mice did not produce normal outgrowths. Ex vivo, C451A-ERα basal cells displayed reduced matrix degradation capacities, suggesting altered migration properties. More importantly, C451A-ERα basal cells recovered in vivo repopulating ability when co-transplanted with wild-type luminal cells and specifically with ERα-positive luminal cells. Transcriptional profiling identified crucial paracrine luminal-to-basal signals. Altogether, our findings uncover an important role for membrane ERα expression in promoting intercellular communications that are essential for mammary gland development.

18F-FDG PET/CT Identifies Predictors of Survival in Patients with Locally Advanced Cervical Carcinoma and Paraaortic Lymph Node Involvement to Allow Intensification of Treatment.

Our objective was to use 18F-FDG PET/CT to identify a high-risk subgroup requiring therapeutic intensification among patients with locally advanced cervical cancer (LACC) and paraaortic lymph node (PALN) involvement. Methods: In this retrospective multicentric study, patients with LACC and PALN involvement concurrently treated with chemoradiotherapy and extended-field radiotherapy between 2006 and 2016 were included. A senior nuclear medicine specialist in PET for gynecologic oncology reviewed all 18F-FDG PET/CT scans. Metabolic parameters including SUVmax, metabolic tumor volume, and total lesion glycolysis (TLG) were determined for the primary tumor, pelvic lymph nodes, and PALNs. Associations between these parameters and overall survival (OS) were assessed with the Cox proportional hazards model. Results: Sixty-eight patients were enrolled in the study. Three-year OS was 55.5% (95% confidence interval, 40.8-68.0). When adjusted for age, stage, and histology, pelvic lymph node TLG, PALN TLG, and PALN SUVmax were significantly associated with OS (P < 0.005). Conclusion:18F-FDG PET/CT was able to identify predictors of survival in the homogeneous subgroup of patients with LACC and PALN involvement, thus allowing therapeutic intensification to be proposed.